Steven H. Woodward

Decreased Anterior Cingulate Volume in Combat-Related PTSD

BACKGROUND Neuroanatomical data point to functional relationships between the anterior cingulate cortex (ACC) and subcortical centers regulating fear, in particular, the amygdala. Functional brain imaging has disclosed divergent patterns of ACC activation in persons with posttraumatic stress disorder (PTSD). In addition, two preliminary structural imaging studies have found evidence of smaller ACC volume in PTSD. We explored associations between PTSD and ACC volume in a relatively large sample of adult combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. METHODS Subjects were US military combat veterans of the Vietnam and Gulf Wars recruited from two metropolitan areas served by allied Department of Veterans Affairs PTSD treatment/research centers. Anterior cingulate cortex volume was analyzed as a function of grouping factors with and without adjustment for body size. RESULTS Posttraumatic stress disorder was associated with smaller anterior cingulate cortex volume. This effect persisted in subjects without histories of alcoholism, did not interact with cohort effects, and was not modified by adjustment for body size. CONCLUSIONS Anterior cingulate cortex volume is substantially smaller in association with combat-related PTSD, a finding broadly consistent with cingulate hypofunctionality in that disorder.

Effects of Moderate-Intensity Exercise on Polysomnographic and Subjective Sleep Quality in Older Adults With Mild to Moderate Sleep Complaints

BACKGROUND This study sought to determine the 12-month effects of exercise increases on objective and subjective sleep quality in initially inactive older persons with mild to moderate sleep complaints. METHODS A nonclinical sample of underactive adults 55 years old or older (n=66) with mild to moderate chronic sleep complaints were randomly assigned to a 12-month program of primarily moderate-intensity endurance exercise (n=36) or a health education control program (n=30). The main outcome measure was polysomnographic sleep recordings, with additional measures of subjective sleep quality, physical activity, and physical fitness. Directional hypotheses were tested. RESULTS Using intent-to-treat methods, at 12 months exercisers, relative to controls, spent significantly less time in polysomnographically measured Stage 1 sleep (between-arm difference=2.3, 95% confidence interval [CI], 0.7-4.0; p=003), spent more time in Stage 2 sleep (between-arm difference=3.2, 95% CI, 0.6-5.7; p=.04), and had fewer awakenings during the first third of the sleep period (between-arm difference=1.0, 95% CI, 0.39-1.55; p=.03). Exercisers also reported greater 12-month improvements relative to controls in Pittsburgh Sleep Quality Index (PSQI) sleep disturbance subscale score (p=.009), sleep diary-based minutes to fall asleep (p=.01), and feeling more rested in the morning (p=.02). CONCLUSIONS Compared with general health education, a 12-month moderate-intensity exercise program that met current physical activity recommendations for older adults improved some objective and subjective dimensions of sleep to a modest degree. The results suggest additional areas for investigation in this understudied area.

Laboratory sleep correlates of nightmare complaint in PTSD inpatients

BACKGROUND Nightmares are rare in the sleep laboratory, even in patients with posttraumatic stress disorder for whom nightmare complaints are diagnostic. Nevertheless, it is possible that laboratory conditions do not preclude the observation of telltales-nightmare-related modifications of tonic sleep-given sufficiently large samples. METHODS Sixty-three unmedicated, nonapneic Vietnam combat veterans undergoing inpatient treatment for posttraumatic stress disorder underwent polysomnographic testing and assessment of nightmare complaint. RESULTS Trauma-related nightmare complaint, but not non-trauma-related complaint, was associated with increased wake-after-sleep-onset in the sleep laboratory. No relationships between nightmare complaint and rapid eye movement sleep architecture were observed. CONCLUSIONS Increased wake-after-sleep-onset was specifically associated with trauma-related nightmare complaint, confirming data from other quarters suggesting they are both phenomenologically and functionally distinct from normal dreaming.

Effects of comorbid diagnoses on sleep disturbance in PTSD

OBJECTIVE Patients with post-traumatic stress disorder (PTSD) are frequently diagnosed with other psychiatric comorbid conditions. This study tested the hypothesis that PTSD patients suffer a greater proportion of sleep problems according to comorbid diagnoses. METHOD National Comorbidity Survey (NCS) data from 591 individuals diagnosed with PTSD were analyzed. Revised versions of the Diagnostic Interview Schedule and Composite International Diagnostic Interview were administered to a representative sample of males and females. Groups consisted of patients diagnosed with lifetime PTSD and with current comorbid panic disorder, major depressive disorder, generalized anxiety disorder, and alcohol dependence. RESULTS Patients diagnosed with PTSD/panic disorder reported a significantly greater proportion of nightmare complaints (96%) and insomnia (100%) compared with the other comorbid groups. CONCLUSIONS A greater proportion of PTSD patients with comorbid panic disorder complain of sleep-related problems than other comorbid groups. This effect appears unique to panic, rather than other general anxiety disorder or depression. Prospective sleep studies are needed to differentiate the role of sleep in PTSD and PD, as well as to examine the role of psychiatric comorbidity in worsening sleep in PTSD patients.

Sleep and depression in combat-related PTSD inpatients

The sleep of 27 unmedicated Vietnam combat-related posttraumatic stress disorder (PTSD) inpatients was monitored for 3 nights. Depressive comorbidity was considered both as a diagnostic category using DMS-III-R criteria, and as a continuous variable using the Beck Depression Inventory (BDI). Data collected included sleep architecture features that have discriminated unipolar depressives from controls in many prior studies, rapid eye movement (REM) sleep latency, and slow-wave sleep time, as well as two additional indices that have sometimes discriminated depressives from controls in waking studies-baseline heart rate and facial electromyography. Structured Clinical Interview for the DSM-III-R (SCID)-diagnosed PTSD+major depressive disorder (MDD) patients failed to exhibit shorter REM latencies, greater REM percents of sleep, or greater REM densities than PTSD-MDD patients, but did exhibit less slow wave sleep. PTSD+MDD patients also exhibited less facial (mentalis) electromyographic activity. REM densities and baseline heart rates were equivocal. REM density, baseline heart rate, and mentalis electromyography all correlated with the BDI, the former two positively, the last, negatively. In summary, SCID-diagnosed PTSD+MDD patients failed to exhibit the classic REM sleep architectural modifications associated with unipolar depression, despite the fact that several other psychophysiologic indices of dysphoria were detectable in their sleep.

Amygdala Volume in Combat-Exposed Veterans With and Without Posttraumatic Stress Disorder: A Cross-sectional Study

CONTEXT Data from animal models demonstrate a link between stress exposure and hypertrophic changes in the amygdala; however, studies of adults with posttraumatic stress disorder (PTSD) have failed to find analogous structural alterations. OBJECTIVES To compare amygdala volumes between a sample of combat veterans with and without PTSD (analysis 1) and examine whether our observation of larger amygdala volume in individuals with PTSD could be accounted for by the presence of trauma exposure in childhood and the severity of combat exposure in adulthood (analysis 2). DESIGN Cross-sectional magnetic resonance imaging. SETTING Veterans Affairs Palo Alto Health Care System Inpatient Trauma Recovery Program and Veterans Affairs New England Health Care System Outpatient PTSD program. PARTICIPANTS Ninety-nine combat-exposed veterans from the Vietnam Conflict or the Persian Gulf War who had been exposed to substantial military operational stress. MAIN OUTCOME MEASURES Amygdala volume adjusted for total cerebral volume, Life Events Checklist, and the Combat Exposure Scale. RESULTS Analysis 1 indicated that combat-exposed individuals with PTSD exhibited larger total amygdala volume compared with their non-PTSD counterparts (99 individuals, P = .047). Analysis 2 indicated that greater severity of combat exposure (87 individuals, P = .02), as well as the interaction between the presence of early life trauma and the severity of combat exposure (87 individuals, P = .008), were significantly associated with smaller total amygdala volume. The PTSD diagnosis continued to explain larger amygdala volume (87 individuals, P = .006). CONCLUSIONS Posttraumatic stress disorder is associated with enlarged amygdala volume, above the variance accounted for by a history of early life trauma and severity of adult trauma exposure. The discrepancy between our and prior findings may be explained by variability in these trauma indices in previous investigations. These findings support additional study of amygdala structure in human stress disorders and further delineation of the role of early and adult trauma on associated neurologic changes.

Subjective versus objective sleep in Vietnam combat veterans hospitalized for PTSD

Twenty-five Vietnam combat veterans with chronic severe posttraumatic stress disorder (PTSD) completed a sleep self-report questionnaire on admission to an inpatient treatment program. Between 1 and 2 months later each spent 3 or more nights in the sleep laboratory. When self-report and laboratory findings were compared, significant relationships were observed between sleep schedule items such as time-to-bed/time-out-of-bed and polysomnographic measures of sleep. In contrast, global ratings of sleep quality were generally unrelated to polysomnographic measures. These findings may have implications for survey research assessing sleep quality in traumatized populations.

Autonomic activation during sleep in posttraumatic stress disorder and panic: a mattress actigraphic study.

BACKGROUND While it has been reported that persons with posttraumatic stress disorder (PTSD) manifest tonic autonomic activation, the literature contains numerous counterexamples. In revisiting the question, this study employed a novel method of mattress actigraphy to unobtrusively estimate heart rate and respiratory sinus arrhythmia over multiple nights of sleep in the home. METHODS Sleep cardiac autonomic status was estimated in four diagnostic groups, posttraumatic stress disorder, panic disorder, persons comorbid for both conditions, and control subjects. All 59 participants were community-residing nonveterans screened for sleep apnea and periodic leg movement disorder with polysomnography. Heart rate and respiratory sinus arrhythmia were calculated from the kinetocardiogram signal measured via accelerometers embedded in a mattress topper. Times in bed and asleep were also estimated. Per participant data were obtained from a median of 12 nights. RESULTS Both posttraumatic stress disorder and posttraumatic stress disorder/panic disorder comorbid groups exhibited significantly higher heart rates and lower respiratory sinus arrhythmia magnitudes than panic disorder participants and control subjects. Panic disorder participants were indistinguishable from control subjects. The PTSD-only group exhibited longer times in bed and longer times presumably asleep than the other three groups. CONCLUSIONS In this study, posttraumatic stress disorder, but not panic disorder, was associated with altered cardiac autonomic status during sleep. Among participants meeting criteria for PTSD alone, autonomic activation co-occurred with prolongation of actigraphic sleep.

Hippocampal volume and declarative memory function in combat-related PTSD

The proposition that declarative memory deficits are systematically related to smaller hippocampal volume was tested in a relatively large sample (n = 95) of U.S. military veterans with and without combat-related posttraumatic stress disorder. This correlative analysis was extended by including multiple measures of verbal and visual declarative memory and multiple memory-relevant regional brain volumes that had been shown to exhibit main effects of PTSD in prior work. Small-to-moderate effects were observed on verbal declarative memory in line with a recent meta-analysis; nevertheless, little or no evidence of systematic linear covariation between memory measures and brain volumes was observed.

Right anterior cingulate cortical volume covaries with respiratory sinus arrhythmia magnitude in combat veterans

Existing data suggest anterior cingulate cortex (ACC) plays a role in autonomic regulation. In persons with posttraumatic stress disorder (PTSD), autonomic regulation appears impaired and smaller mean ACC volume has been reported. This study examined relationships between ACC volume and the magnitude of respiratory sinus arrhythmia (RSA) in 77 U.S. combat veterans at rest, 40 of whom met criteria for PTSD. RSA magnitude did not differ in combat survivors with and without PTSD, which contradicts studies comparing civilians with PTSD to nontraumatized controls. RSA magnitude was positively correlated with right but not left hemisphere ACC volume. This finding was statistically independent of the presence or absence of PTSD.